Secretome is known as condition medium refers to the used/ waste/ spent medium of cultured cells collected after specific incubation time and condition. Secretome has a variety of benefits in the treatment of various diseases and plays an important role as a therapeutic agent in dealing with various skin problems. The main factor that plays a role is the secreted protein, which can help repair and regenerate damaged tissue.

Secretome is considered a bioactive molecule secreted by cells that contains proteins including growth factors, cytokines, chemokines and ECM including microvesicles and exosomes that can stimulate various biological reactions. The use of secretome can enhance cell proliferation, differentiation, migration and tissue repair. Secretome also can be useful for drug delivery systems due to its homing capabilities that can be specific and targeted compound release into problems area. Secretome can be isolated from various cell types especially Mesenchymal stem cells (MSC) including isolated from bone marrow (BM), adipose tissue and umbilical cord or Wharton’s jelly. The umbilical cord or Wharton jelly is the easiest obtainable cell source which has known with low immunogenicity thus give advantages to wound healing process for allogenic application.

Secretome was collected after the cells being incubate with serum-free medium or cultured in hypoxic conditions. Culturing the cells with hypoxic condition can enhance the proliferation and migration effects of skin cells; keratinocytes and dermal fibroblasts. Compared to normoxia condition, hypoxic condition can upregulate the angiogenesis factors and increased collagen production. Secretome from MSC contains various ECM components (e.g. collagen, fibronectin, lumican, periostin), growth factors (e.g. bFGF, TGF-β1, pigment epithelium-derived factor), and interestingly, the factors also have anti-inflammatory, antifibrotic and immunomodulatory actions. The most common secreted factors are VEGF, PDGF, Hepatocyte growth factor, bFGF, Macrophage stimulating protein, Keratinocyte growth factor, Insulin-like growth factor 1 (IGF-1), and many more. These secreted factors play essential role in regeneration and angiogenesis during healing process.

Recently, a study indicated that secretomes had significant effect on promoting normal skin regeneration, inhibiting fibrosis and restoring the appearance and function of damage skin. Wound healing is a natural process of the body that repairs and regenerates damaged tissues and consists of three main phases—inflammation, proliferation, and remodeling that occur in overlap. Wound treatment with secretome was able to accelerated wound healing by increasing the effect of cell migration and proliferation and triggering angiogenesis, re-epithelialization, neovascularization and deposition of collagen.

Secretomes involves in the collagen synthesis and potentially can be used for preventing UV-induced skin damage. Ultraviolet (UV) radiation can cause skin problems such as photoaging. Photoaging is skin aging that caused by excessive UV exposure that causes skin morphological and physiological changes such as the appearance of wrinkles and reduce skin elasticity. UV radiation also can cause inhibition of the cell proliferation rate and reductions of collagen I, collagen III and elastin due to downregulation of expression of mRNA and can trigger the apoptosis of skin cells, so as to inhibit skin regeneration and be able to inflict DNA damage in keratinocytes. The recent study shows that secretomes derived from MSCs can increased the cells proliferation, decreased the amount of cell apoptosis and cellular aging, increased collagen synthesis as well as inhibit the production MMP1 in skin cells. Secretomes also can be used as an active ingredient in cosmetics that benefits in regenerating the skin, reducing the wrinkles and increased skin moisture.  

There is also a condition of hair loss (alopecia) due to abnormalities in the scalp that causes the active phase of hair growth to be inhibited. Some study shows the result of the use of secretome can activate the Wnt/β-catenin signaling pathway that play a role in trigger the proliferation and increase hair follicle cells growth. Secretome is reported to have antimicrobial activity that can suppress the growth of microbes. Secretome is known to release antimicrobial peptides such as cathelicidin LL-37, calprotectin, hepcidin, RNase3, lipocalin-2 and human β-defensins. The use of secretome can be one of the alternatives to prevent drug resistance.

Secretome, a bioactive factor secreted by MSCs, has a variety of benefits on the skin as a therapeutic agent. There are several advantages of secretomes compared to the use of cells where it can be manufactured and formulated in various form depending on the suitability, application, and can be packed or transported more easily. From a future perspective, MSCs secretomes could be viewed as part of a potential delivery system within nanomedicine, allowing us to specifically target the skin problems. For the purpose of the challenging current applications, the development of standardized secretome isolation, purification, safety, storage and quality need to be investigate. Furthermore, the dose and route of secretome administration must also be clearly determined. Thus, more preclinical and clinical studies are required for using of MSCs secretome in clinical applications.

Reference

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Md Fadilah NI, Mohd Abdul Kader Jailani MS, Badrul Hisham MA, Sunthar Raj N, Shamsuddin SA, Ng MH, Fauzi MB, Maarof M. Cell secretomes for wound healing and tissue regeneration: Next generation acellular based tissue engineered products. Journal of Tissue Engineering. 2022 Jul; 13:20417314221114273.

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